Investigation Of The Clinicopathological Features, Immunophenotypes And Bcl-6 Gene Rearrangement Of The Primary Central Nervous System Lymphoma

Primary central nervous system lymphoma (PCNSL) is an extranodal form of non-Hodgkin lymphoma arising in the craniospinal axis and characterized by a marked degree of clinical and morphologic heterogeneity. It constitutes only 1.0 to 1.5% of all brain tumors. Their incidence has gone up over tenfold in the last 20 years. Though, there has been an association of PCNSL with acquired immune deficiency syndrome (AIDS), yet the increased incidence of PCNSL appears to be real and unrelated to AIDS and organ transplantation. This increased incidence is not all because of improvement in diagnostic technology and practice. The outcome remains gloomy despite surgical resection, radiotherapy and chemotherapy regimens. The pathogenesis of PCNSL is unknown. A novel candidate proto-oncogene, bcl-6, that is involved in chromosome band 3q27 aberrations in NHL has been recently identified. Findings support the hypothesis of a germinal centerB cell-derived origin of PCNSL, indicate a significant role of bcl-6 gene in the pathogenesis of PCNSL. The purpose of this study was to assess the clinical features, neuroradiological findings, pathology, and to investigate the histogenetic origin of PCNSL with respect to bcl-6 gene rearrangement and to identify prognostic markers in a cohort of patients with PCNSL in China.This study present a retrospective analysis of 35 patients with PCNSL treated at the department of neurosurgery, West China Hospital, Sichuan University between January 1997 and October 2002, for whom archival tumor tissue was available. Analysis of patients with PCNSL documents the clinic features, neuroradiological findings, and histological characteristics. The histological diagnosis was obtained after surgical resection; CT and MRI studies were accomplished before operation. Categorical factors influencing survival were examined by the Kaplan-Meier estimator and groups compared with the log rank test. The lymphomas were morphologically subclassified according to criteria of the World Health Organization classification of haemotopoietic and lymphoid tissues. Immunohistochemistry for the following antigens was performed: LCA, CD20, CD45RO, PC and GFAP. Semi-nested polymerase chain reaction to detect bcl-6 gene rearrangement was performed in paraffin embedded tissue sections from 23 patients who had surgically resected PCNSL.The cohort included 19 men and 16 women whose median age at diagnosis was 52 years old. There are no pathognomonic presenting symptoms or signs. No patient had antecedent of AIDS or acquired immunodeficiency syndrome. Most of the lesions are hyperdense or isodense (92%) on CT, hypointense or isointense on T1-weighted images, andhypointense or isointense on T2-weighted images. Nearly all the lesions enhance after contrast uptake. Calcification, haemorrhage or necrosis is scarce. All lymphomas met the diagnostic morphological and phenotypic. All of the 35 tumors were LCA+, 32 of 35 tumors were CD20+, 2 tumors were PC+, only 1 tumor was CD45RO +, and 0 of 32 tumors were GFAP+. Rearranged bcl-6 gene was found in 6 cases with semi-nested polymerase chain reaction, rearrangement of bcl-6 gene was not significantly associated with longer overall survival.PCNSL is likely to constitute more than one disease entity, as suggested by the heterogeneity of morphology, clinical presentation, and response to treatment. Although PCNSL in immunocompetent patients have a variable neuroradiological appearance, the imaging data often suggest the diagnosis. Semi-nested polymerase chain reaction assay established for determination of bcl-6 gene rearrangement in PCNSL is a rapid and sensitive method.It can be concluded that junctional sequences created by chromosomal translocations in PCNSL, which involve immunoglobulin gene and putative bcl-6 gene on reciprocal partner chromosomes, are unique to neoplastic cells characterized by particular histological and immunological phenotypes. Our results suggest translocation-mediated bcl-6 oncogene activation as a so far unknown pathogenetically relevant mechanism in PCNSL. The difference was not statistically significant between bcl-6 gene rearrangement and a more favorable outcome in patients with PCNSL.